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LINC02418 upregulates EPHA2 by competitively sponging miR-372-3p to promote 5-Fu/DDP chemoresistance in colorectal cancer

Chemoresistance is a huge clinical challenge in the treatment of advanced colorectal cancer (CRC). Non-coding RNAs (ncRNAs) and messenger RNA (mRNA) are involved in CRC chemoresistance. However, the profiles of long ncRNAs (lncRNAs), microRNAs (miRNAs), mRNAs and competing endogenous RNA (ceRNA) net...

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Autores principales: Yao, Fei, Huang, Xiaoying, Xie, Zhufu, Chen, Jie, Zhang, Ling, Wang, Qiang, Long, Hui, Jiang, Jue, Wu, Qingming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587682/
https://www.ncbi.nlm.nih.gov/pubmed/35914269
http://dx.doi.org/10.1093/carcin/bgac065
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author Yao, Fei
Huang, Xiaoying
Xie, Zhufu
Chen, Jie
Zhang, Ling
Wang, Qiang
Long, Hui
Jiang, Jue
Wu, Qingming
author_facet Yao, Fei
Huang, Xiaoying
Xie, Zhufu
Chen, Jie
Zhang, Ling
Wang, Qiang
Long, Hui
Jiang, Jue
Wu, Qingming
author_sort Yao, Fei
collection PubMed
description Chemoresistance is a huge clinical challenge in the treatment of advanced colorectal cancer (CRC). Non-coding RNAs (ncRNAs) and messenger RNA (mRNA) are involved in CRC chemoresistance. However, the profiles of long ncRNAs (lncRNAs), microRNAs (miRNAs), mRNAs and competing endogenous RNA (ceRNA) networks in CRC chemoresistance are still largely unknown. Here, we compared the gene expression profiles in chemosensitive (HCT8) and chemoresistant [HCT8/5-fluorouracil (5-Fu) and HCT8/cisplatin (DDP)] cell lines by whole-transcriptome sequencing. The common differentially expressed RNAs in two drug-resistant cells were selected to construct lncRNA–miRNA–mRNA networks. The ceRNA network closely related to chemoresistance was further established based on the widely accepted drug resistance-associated genes enriched in three signaling pathways involved in chemoresistance. In total 52 lncRNA–miRNA–mRNA pathways were screened out, among which EPHA2 and LINC02418 were identified as hub genes; thus, LINC02418/miR-372-3p/EPHA2 were further selected and proved to affect the 5-Fu and DDP resistance of CRC. Mechanistically, LINC02418 upregulated EPHA2 by functioning as a ‘sponge’ of miR-372-3p to modulate the chemoresistance of CRC. Collectively, our study uncovered the underlying mechanism of LINC02418/miR-372-3p/EPHA2 in 5-Fu and DDP resistance of CRC, which may provide potential therapeutic targets for improving the chemosensitivity of CRC.
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spelling pubmed-95876822022-10-25 LINC02418 upregulates EPHA2 by competitively sponging miR-372-3p to promote 5-Fu/DDP chemoresistance in colorectal cancer Yao, Fei Huang, Xiaoying Xie, Zhufu Chen, Jie Zhang, Ling Wang, Qiang Long, Hui Jiang, Jue Wu, Qingming Carcinogenesis Carcinogenesis Chemoresistance is a huge clinical challenge in the treatment of advanced colorectal cancer (CRC). Non-coding RNAs (ncRNAs) and messenger RNA (mRNA) are involved in CRC chemoresistance. However, the profiles of long ncRNAs (lncRNAs), microRNAs (miRNAs), mRNAs and competing endogenous RNA (ceRNA) networks in CRC chemoresistance are still largely unknown. Here, we compared the gene expression profiles in chemosensitive (HCT8) and chemoresistant [HCT8/5-fluorouracil (5-Fu) and HCT8/cisplatin (DDP)] cell lines by whole-transcriptome sequencing. The common differentially expressed RNAs in two drug-resistant cells were selected to construct lncRNA–miRNA–mRNA networks. The ceRNA network closely related to chemoresistance was further established based on the widely accepted drug resistance-associated genes enriched in three signaling pathways involved in chemoresistance. In total 52 lncRNA–miRNA–mRNA pathways were screened out, among which EPHA2 and LINC02418 were identified as hub genes; thus, LINC02418/miR-372-3p/EPHA2 were further selected and proved to affect the 5-Fu and DDP resistance of CRC. Mechanistically, LINC02418 upregulated EPHA2 by functioning as a ‘sponge’ of miR-372-3p to modulate the chemoresistance of CRC. Collectively, our study uncovered the underlying mechanism of LINC02418/miR-372-3p/EPHA2 in 5-Fu and DDP resistance of CRC, which may provide potential therapeutic targets for improving the chemosensitivity of CRC. Oxford University Press 2022-08-01 /pmc/articles/PMC9587682/ /pubmed/35914269 http://dx.doi.org/10.1093/carcin/bgac065 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Carcinogenesis
Yao, Fei
Huang, Xiaoying
Xie, Zhufu
Chen, Jie
Zhang, Ling
Wang, Qiang
Long, Hui
Jiang, Jue
Wu, Qingming
LINC02418 upregulates EPHA2 by competitively sponging miR-372-3p to promote 5-Fu/DDP chemoresistance in colorectal cancer
title LINC02418 upregulates EPHA2 by competitively sponging miR-372-3p to promote 5-Fu/DDP chemoresistance in colorectal cancer
title_full LINC02418 upregulates EPHA2 by competitively sponging miR-372-3p to promote 5-Fu/DDP chemoresistance in colorectal cancer
title_fullStr LINC02418 upregulates EPHA2 by competitively sponging miR-372-3p to promote 5-Fu/DDP chemoresistance in colorectal cancer
title_full_unstemmed LINC02418 upregulates EPHA2 by competitively sponging miR-372-3p to promote 5-Fu/DDP chemoresistance in colorectal cancer
title_short LINC02418 upregulates EPHA2 by competitively sponging miR-372-3p to promote 5-Fu/DDP chemoresistance in colorectal cancer
title_sort linc02418 upregulates epha2 by competitively sponging mir-372-3p to promote 5-fu/ddp chemoresistance in colorectal cancer
topic Carcinogenesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587682/
https://www.ncbi.nlm.nih.gov/pubmed/35914269
http://dx.doi.org/10.1093/carcin/bgac065
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